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Alcohol excites Cerebellar Golgi Cells by inhibiting the Na+/K+ ATPase (Botta et al.2010)
Accession: 127021
Patch-clamp in cerebellar slices and computer modeling show that ethanol excites Golgi cells by inhibiting the Na+/K+ ATPase. In particular, voltage-clamp recordings of Na+/K+ ATPase currents indicated that ethanol partially inhibits this pump and this effect could be mimicked by low concentrations of the Na+/K+ ATPase blocker ouabain. The partial inhibition of Na+/K+ ATPase in a computer model of the Golgi cell reproduced these experimental findings that established a novel mechanism of action of ethanol on neural excitability.
Reference: Botta P, de Souza FM, Sangrey T, De Schutter E, Valenzuela CF (2010) Alcohol excites cerebellar Golgi cells by inhibiting the Na(+)-K(+) ATPase. Neuropsychopharmacology 35:1984-96 [PubMed]
Citations  Citation Browser
Model Information (Click on a link to find other models with that property)
Model Type:  Neuron or other electrically excitable cell; Electrogenic pump;
Brain Region(s)/Organism:  Cerebellum;
Cell Type(s):   Cerebellar golgi cell;
Channel(s):  Na/K pump;  
Gap Junctions:  
Receptor(s):  
Gene(s):  
Transmitter(s):  
Simulation Environment:  Neuron;
Model Concept(s):  Detailed Neuronal Models;
Implementer(s):  de Souza, Fabio M S [fabios at base.com.br];
Search NeuronDB for information about:  Na/K pump;
Model files   Download zip file   Auto-launch             Help downloading and running models
\
Golgi_cell_NaKATPAse
sessions
SimData
README.html
Screenshot20100716_4.02.55PM.png
Golgi_CALC.mod
Golgi_CALC_ca2.mod
Golgi_Ca_HVA.mod
Golgi_Ca_LVA.mod
Golgi_hcn1.mod
Golgi_hcn2.mod
Golgi_KA.mod
Golgi_KM.mod
Golgi_KV.mod
Golgi_lkg.mod
Golgi_Na.mod
Golgi_NaP.mod
Golgi_NaR.mod
Golgi_SK2.mod
K_conc.mod
Na_conc.mod
Pregen.mod
pump.mod
Golgi_BK.mod
Synapse.mod
Golgi_template.hoc
Channel_dynamics.hoc
Save_data.hoc
Golgi_ComPanel.hoc
Start_Golgi_Ouabain.hoc
mosinit.hoc
Synapses.hoc
utils.hoc
Golgi_Pump_Ouabain.ses
Golgi_count.txt
nerst
                            
/*******Cerebellar Golgi Cell Model with Na+/K+ ATPase**********

Developers:    Fabio M Simoes de Souza & E De Schutter

Work Progress: July 2009 - Dec 2009

Developed At:  Okinawa Institute of Science and Technology
               Computational Neuroscience Unit
               Okinawa - Japan
	       
Model Published in: 

             Botta P, Simoes de Souza F, Sangrey T, De Schutter E,
             Valenzuela F (2010) Alcohol excites cerebellar Golgi
             cells by inhibiting the Na+/K+ ATPase.
             Neuropsychopharmacology 35: 1984-1996.

This script is a modification from a previous published GoC model
(Solinas et al., 2007). A Na+/K+ ATPase and ionic concentration pools
for Na+, K+, Ca2+ were incorporated into the soma of the model.
The equations that simulated the Na+/K+ ATPase are described in Table
S10 of Takeuchi et al. (2006)

Abstract

Alcohol Excites Cerebellar Golgi Cells by Inhibiting the Na+/K+ ATPase
Patch-clamp in cerebellar slices and computer modeling show that
ethanol excites Golgi cells by inhibiting the Na+/K+ ATPase. In
particular, voltage-clamp recordings of Na+/K+ ATPase currents
indicated that ethanol partially inhibits this pump and this effect
could be mimicked by low concentrations of the Na+/K+ ATPase blocker
ouabain. The partial inhibition of Na+/K+ ATPase in a computer model
of the Golgi cell reproduced these experimental findings that
established a novel mechanism of action of ethanol on neural
excitability.

Reference: Botta P, de Souza FM, Sangrey T, De Schutter E, Valenzuela
CF (2010) Alcohol excites cerebellar Golgi cells by inhibiting the
na(+)-k(+) ATPase. Neuropsychopharmacology 35:1984-96

Usage instructions:

Auto-launch from ModelDB or download and extract the archive.  Then
under:

----
MSWIN

run mknrndll, cd to the archive and make the nrnmech.dll.  Then double
click on the mosinit.hoc file.

----
MAC OS X

Drag and drop the Golgi_cell_NaKATPAse folder onto the mknrndll icon.
Drag and drop the mosinit.hoc file onto the nrngui icon.

----
Linux/Unix

Change directory to the Golgi_cell_NaKATPAse folder. run
nrnivmodl. Then type nrngui mosinit.hoc

----

Once the simulation is started click the button labeled 
"Figure 7g from Botta et al. 2010" The simulation will produce a
result similar to figure 7g from the paper:

screenshot

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